After analyzing data from more than 1 million participants, researchers have identified more than 100 genes associated with anxiety. These genes not only contribute to the development of anxiety disorders but are also linked to other mental and physical health conditions, such as depression and gastrointestinal disorders.
Anxiety disorders and their symptoms are mental health problems that affect many people around the world, impairing not only emotional health but also quality of life. These disorders can cause a range of difficulties, such as constant fear, excessive worry, and tension that make it difficult to carry out normal daily activities.
When someone suffers from anxiety, their ability to work, maintain healthy relationships, or even enjoy leisure time can be seriously affected.
Anxiety can manifest itself in many different ways, from panic attacks, where the person feels an intense sense of fear and physical discomfort, to persistent worries that consume their thoughts. These symptoms vary greatly from one person to another, which makes treatment more challenging.
In recent years, scientists have been studying how genes can influence a person’s risk of developing anxiety. This means that genetics—the set of information we inherit from our parents—may play a role in determining who is most vulnerable to this type of problem, as well as in developing treatments that take into account each patient’s individual characteristics.
By better understanding which genetic factors increase someone’s chances of developing anxiety, doctors and researchers can develop more targeted and effective treatments.
Researchers from the Yale Department of Psychiatry examined the genetic profiles of more than 1.2 million participants, including 97,383 cases, to investigate the genetics of anxiety disorders in five continental groups, the results of which were published in Nature Genetics.
Through ancestry-specific and cross-ancestry genome-wide association studies, they identified 51 loci associated with anxiety, 39 of which were novel. In addition, polygenic risk scores derived from individuals of European ancestry were associated with anxiety in African, mixed-race American, and East Asian groups.
Heritability of anxiety was enriched for genes expressed in the limbic system, cerebral cortex, cerebellum, metencephalon, entorhinal cortex, and brainstem. Transcriptome-wide and proteome-wide analyses highlighted 115 genes associated with anxiety through brain-specific and cross-tissue regulation.
Anxiety also showed global and local genetic correlations with depression, schizophrenia, bipolar disorder, and generalized pleiotropy with multiple domains of physical health.
Overall, this study expands our knowledge of the genetic risk and pathogenesis of anxiety disorders, highlighting the importance of investigating diverse populations and integrating multi-omic information.
“This effort highlights the power of large-scale genetic studies to dissect the complex pathogenesis of anxiety by demonstrating how multiple genes acting on different brain functions contribute to defining individual genetic risk,” said Renato Polimanti, Ph.D., associate professor of psychiatry at Yale School of Medicine and senior author of the study.
These findings open new possibilities for understanding the molecular basis of psychopathology and assessing the mechanisms responsible for the comorbidity between anxiety and other negative health outcomes. They also noted that some genes associated with anxiety may also predispose to other mental illnesses, including depression, schizophrenia, and bipolar disorder.
In line with the comorbidity of anxiety with physical health, the study also demonstrated that genetic risk for anxiety is also correlated with non-psychiatric conditions. In particular, the strongest evidence was observed for gastrointestinal disorders and pain-related outcomes.
“By studying anxiety disorders across five different ancestries for the first time, we were able to uncover the genetic architecture of anxiety disorders with the most powerful genetic association,” said Eleni Friligkou, MD, one of the study’s authors.
Overall, this study expands our knowledge of the genetic risk and pathogenesis of anxiety disorders, highlighting the importance of investigating diverse populations and integrating multi-omics information.
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Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study
Friligkou, E., Løkhammer, S., Cabrera-Mendoza, B. et al.
Abstract:
We leveraged information from more than 1.2 million participants, including 97,383 cases, to investigate the genetics of anxiety disorders across five continental groups. Through ancestry-specific and cross-ancestry genome-wide association studies, we identified 51 anxiety-associated loci, 39 of which were novel. In addition, polygenic risk scores derived from individuals of European descent were associated with anxiety in African, admixed American and East Asian groups. The heritability of anxiety was enriched for genes expressed in the limbic system, cerebral cortex, cerebellum, metencephalon, entorhinal cortex and brain stem. Transcriptome-wide and proteome-wide analyses highlighted 115 genes associated with anxiety through brain-specific and cross-tissue regulation. Anxiety also showed global and local genetic correlations with depression, schizophrenia and bipolar disorder and widespread pleiotropy with several physical health domains. Overall, this study expands our knowledge regarding the genetic risk and pathogenesis of anxiety disorders, highlighting the importance of investigating diverse populations and integrating multi-omics information.
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